Non-absorbable, biocompatible polymers play an invaluable role in the surgical treatment and medical care of patients with a variety of ailments. Most commonly, non-absorbable biocompatible polymers are used in a variety of medical devices including sutures, and prosthetic meshes for hernia and pelvic floor repair, wherein at least a portion of these devices remains in the body to provide necessary permanent reinforcement of tissue. Surgical meshes have indeed become the standard of care in hernia repair and pelvic floor repair procedures, providing the necessary strength and structure to reinforce compromised tissues resulting in a permanent tension free repair of the anatomical defect. Turning to surgical wound closure, certain monofilament and braided sutures are comprised of non-absorbable biocompatible polymers and are commonly used to provide permanent fixation for blood vessel anastomosis, heart valve repair, and orthopedic uses including tendon repair and deep tissue closure among other conventional applications and uses.
As with all surgical procedures, surgical wounds incorporating non-absorbable polymer reinforcements, such as sutures or meshes, may be prone to infection. Moreover, it has been long known that non-absorbable implantable materials, even though provided for use in a sterile state, may serve as a nidus for infection by providing a substrate for bacterial attachment, colonization and biofilm formation. Such biofilms, once established, can be extremely resistant to treatment with conventional and available antibiotics and can be life threatening or may otherwise result in protracted long term suffering for the inflicted patient. Infected surgical wounds that have resisted treatment from antibiotics are commonly re-operated upon to access and remove non-absorbable implantable materials and clear the infection before a new prosthetic is implanted to enable the healing process to commence again. Such procedures often require protracted hospital stays, with substantial costs and considerable suffering to the patient as well as the risks attendant with any surgical procedure.
Antimicrobial agents presently used for bioabsorbable polymers may be insufficient for non-absorbable polymer implants. Although it is believed that biofilm formation on bioabsorbable polymers may occur to a lesser degree as well, due to the transient nature of the absorbable polymer substrate supporting the bacterial attachment, these infections are easier to treat and ultimate removal of the bioabsorbable polymers implants are rarely necessary as they will naturally metabolize and leave the body with time. As such, a short-term antimicrobial agent that remains active for durations spanning hours to days may be more acceptable as a prophylactic solution for absorbable implants.
In comparison, with non-absorbable implants if bacteria contamination should survive an initial short acting antimicrobial agent, it would tend to progress and grow unimpeded using surfaces of the non-absorbable implants as an attachment substrate. In such cases, patients when seen by their physicians several weeks to several months after surgery are observed to have indications of infection. It has even been proposed that the initial source of such infection was likely not encountered during the surgical procedure in these cases, but was rather introduced systemically through the circulatory system during a later event. In these scenarios, a short term antimicrobial agent designed to inhibit the growth of bacteria introduced during surgery may be ineffective.
As such, in addition to the potent but short acting antimicrobial effect that may used for bioabsorbable polymer implants, non-absorbable implants may require a long acting efficacy against bacteria colonization and biofilm formation on their surfaces.
The use of combination medical devices that consist of both bioabsorbable and non-absorbable polymeric components is increasing in the medical arts. In particular, hernia meshes that incorporate a bioabsorbable film or fabric on at least one side can be used to inhibit the formation of connective tissue adhesions between internal organs and the surface of the implanted mesh. Since it is known that connective tissue adhesions result in multiple complications, including long term pain, reduction in mobility of patient, and difficulty for the surgeon should future operations be required, these combinational products address an important need. However, when considering surgical site infections, the antimicrobial agent that may be best suited for the bioabsorbable component may not be best suited for the non-absorbable component. For the non-absorbable component, a long-lasting or even permanent antimicrobial surface is desirable for all of the reasons described above. However, for the bioabsorbable component, it may be important that the antimicrobial agent is also bioabsorbable and preferably absorbable at a rate equal to or greater than the absorption rate or degradation rate of the bioabsorbable polymer. In the case of hernia mesh devices, the tissue separating bioabsorbable layer of the mesh can absorb quite rapidly. For example, tissue separating materials such as oxidized regenerated cellulose may absorb and/or degrade within two weeks or less. For these combination products, there is a need for a fast-acting, fast absorbing antimicrobial agent in combination with a long-lasting antimicrobial agent for surface protection for the underlying nonabsorbable mesh.
To date, the combination of both a rapidly diffusing antimicrobial agent, that can provide an initial offensive attack against bacteria entrained in the wound during the surgical procedure, and an antimicrobial agent providing long lasting inhibition against bacteria colonization at an implant surface has not been disclosed. Also not disclosed are unique microstructures of such combinational coatings that provide for antimicrobial agents to act effectively and simultaneously from the time of implantation while allowing at least one long term antimicrobial agent to remain attached to the surfaces of the medical device to prevent bacterial attachment for a long term. Furthermore, the use of fast acting, long-ranging antimicrobials (producing a large “zone of inhibition”) in the bioabsorbable component of combinational implants along with long-lasting antimicrobials that provide long term protection against surface colonization of the non-absorbable component of the implant has not been described or disclosed.
Therefore, there is a continuing need in this art for novel antimicrobial coatings for implantable medical devices.